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World J Hepatol. Mar 27, 2023; 15(3): 364-376
Published online Mar 27, 2023. doi: 10.4254/wjh.v15.i3.364
May 2022 acute hepatitis outbreak, is there a role for COVID-19 and other viruses?
Reem Elbeltagi, Mohammed Al-Beltagi, Nermin Kamal Saeed, Adel Salah Bediwy, Osama Toema
Reem Elbeltagi, Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
Mohammed Al-Beltagi, Osama Toema, Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Al Gharbia, Egypt
Mohammed Al-Beltagi, Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
Nermin Kamal Saeed, Department of Pathology, Microbiology Section, Salmaniya Medical Complex, Manama 12, Bahrain
Nermin Kamal Saeed, Department of Microbiology, Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
Adel Salah Bediwy, Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Al Gharbia, Egypt
Adel Salah Bediwy, Department of Chest Diseases, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
Author contributions: Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS, Toema O collected the data and wrote and revised the manuscript.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammed Al-Beltagi, MBChB, MD, MSc, PhD, Academic Editor, Chairman, Consultant Physician-Scientist, Professor, Researcher, Department of Pediatrics, Faculty of Medicine, Tanta University, Al Bahr Street, Tanta 31511, Al Gharbia, Egypt. mbelrem@hotmail.com
Received: October 21, 2022
Peer-review started: October 21, 2022
First decision: January 3, 2023
Revised: January 6, 2023
Accepted: March 14, 2023
Article in press: March 14, 2023
Published online: March 27, 2023
Abstract

There has been an increasing number of reported cases of acute hepatitis of unknown origin in previously healthy children since first reported on March 31, 2022. This clinical syndrome is identified by jaundice and markedly elevated liver enzymes with increased aspartate transaminase and/or alanine aminotransaminase (greater than 500 IU/L). We conducted an inclusive literature review with respect to acute hepatitis outbreaks in children using the search terms acute hepatitis, outbreak, children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and adenovirus. According to the cumulative data presented in four main studies, the median age is 4 years, with a male predominance (1.3:1). Jaundice was the most common clinical manifestation (69%), followed by vomiting (63%), anorexia (52.9%), diarrhea (47.2%), abdominal pain (39%), pyrexia (33.3%), pale stool (30%), and dark urine (30%). Coryza and lethargy were reported in 16.6%, while pruritus was reported in 2% of cases. Acute liver failure was observed in 25% of cases. The exact mechanism of this acute hepatitis outbreak is still not entirely clear. Adenoviruses and SARS-CoV-2 were detected in a significant number of patients. Coinfection with adenovirus and SARS-CoV-2 could be a possible underlying mechanism. However, other possible infections and mechanisms must be considered in the pathogenesis of this condition. Acute hepatitis of unknown origin in children has been a serious problem since the start of the COVID-19 pandemic but has not yet been sufficiently addressed. Many questions remain regarding the underlying mechanisms leading to acute liver failure in children, and it is likely that extensive future research is needed.

Keywords: Acute hepatitis of unknown origin, Children, Adenovirus, SARS-CoV-2, COVID-19, Hepatic failure

Core Tip: There has been an increasing number of acute hepatitis of unknown origin in children since first reported on March 31, 2022. The exact mechanism of this acute hepatitis outbreak is still unclear. Still, the increased detection rate of adenoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may imply a key role for these viruses in the pathogenesis of this childhood condition. Coinfection with adenovirus and SARS-CoV-2 could also play a role, but comprehensive research is still needed to reach an exact mechanism. Until an aetiology is uncovered, the focus should be placed on the prevention of this syndrome in children via the use of proper hygiene.